Light chain 3 immunoexpression in psoriasis.

Autophagy dysregulation is involved in many diseases. The implication of autophagy in psoriasis pathogenesis is still uncertain. To investigate the role of Light Chain 3 (LC3), a good marker for autophagy, in psoriatic skin based on immunohistochemical study and correlate its expression - for the first time to the best of our knowledge - to clinicopathological data Prospective case-control study was conducted on 60 subjects (30 control, 30 psoriasis patients). Skin biopsies from control, lesional, and perilesional skin were processed for routine histopathological examination and LC3 immunoreaction assessment. There was a significant upregulation of the epidermal and dermal LC3 immunoreaction in the lesional skin compared with the control and perilesional skin specimens (P < .001). A significant positive correlation between the epidermal and dermal LC3 H scores in the lesional and perilesional skin was recorded. There was a non-significant relationship between the H score in the lesional skin and disease severity. LC3 could be considered in psoriasis pathogenesis; however, LC3 was not related to the severity of the disease. The findings might offer a novel target therapy for psoriasis patients.

Countering adipose tissue dysfunction could underlie the superiority of telmisartan in the treatment of obesity-related hypertension.

BACKGROUND: The prevalence of hypertension and obesity has increased significantly in recent decades. Hypertension and obesity often coexist, and both are associated with increased cardiovascular mortality. Obese hypertensive patients usually require special anti-hypertensive treatment strategy due to the increased risk of treatment resistance. Molecules that can target both obesity and hypertension underlying pathologies should get more attention. Herein, we evaluated the therapeutic effects of telmisartan, with special interest in visceral adipose tissue dysfunction, in obesity-related hypertension rat model. METHODS: Thirty male Wistar rats weighing 150-200 g were equally divided into: 1-Control group (fed normal laboratory diet for 24 weeks), 2-Diet-induced obesity group (DIO, fed high fat diet for 24 weeks), and 3-Diet-induced obesity treated with telmisartan group (DIO + Tel, fed high fat diet and received telmisartan for 24 weeks). At the end of the study, anthropometrical parameters were evaluated. Systolic blood pressure and heart rate were measured. Blood samples were collected for the measurement of serum lipids, adipokines, cardiac, renal, inflammatory, and oxidative stress biomarkers. Kidneys were removed and used for histopathological studies, and visceral adipose tissue was utilized for histopathological, immunohistochemical and RT-PCR studies. RESULTS: High fat diet resulted in obesity-related changes in anthropometrical parameters, elevation of blood pressure, increase in heart rate, higher serum levels of cardiac, inflammatory and kidney function biomarkers, with altered serum lipids, adipokines and oxidative stress markers. Morphological changes (H&E and PAS-stained sections) were noticed in kidneys and visceral adipose tissue. Immunohistochemistry and RT-PCR studies confirmed adipose tissue dysfunction and over-expression of inflammatory and oxidative stress proteins. Telmisartan countered obesity-induced alterations in cardiovascular, renal, and adipose tissue functions. CONCLUSION: Adipose tissue dysfunction could be the core pathophysiology of obesity-related hypertension. Besides its anti-hypertensive effect, telmisartan had profound actions on visceral adipose tissue structure and function. Attention should be given to polymodal molecules targeting adipose tissue-related disorders.

Therapeutic potential of targeted-gold nanospheres on collagen-induced arthritis in rats.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes functional disability due to bone destruction and severe joint pain. Current anti-rheumatic treatments develop severe complications and do not provide complete remission. Gold nanoparticles (AuNPs) have garnered attention because of their unique physical and chemical properties. In this study, we have evaluated the therapeutic effects of gold nanospheres (AuNSs) with two different ligands (targeted-nanoparticles) against collagen-induced arthritis (CIA) and compared the outcomes with conventional methotrexate (MTX) and biological (infliximab) treatments. Clinical evaluation was performed by radiographic and histological examinations. The bioaccumulation of AuNSs in vital organs was assessed. The mechanistic studies targeting pro-inflammatory/anti-inflammatory and angiogenic mediators' expressions were performed. Radiographic examination showed that the targeted AuNSs reduced joint space narrowing and bone erosion. Moreover, histopathological examination of rat ankle joints demonstrated that targeted AuNSs reduce bone and cartilage degeneration/inflammation. Gold nanospheres-conjugated with nucleus localized peptide (nuclear membrane-targeted) (AuNSs@NLS) has resolved bone destruction and inflammation compared to gold nanospheres-conjugated at polyethylene glycol (AuNSs@PEG). Although the AuNSs accumulated in different organs in both cases, they did not induce any toxicity or tissue damage. The two different targeted AuNSs significantly suppress inflammatory and angiogenic mediators' expression and induced anti-inflammatory cytokine production, but the AuNSs@NLS had superior therapeutic efficacy. In conclusion, these results suggested that nuclear membrane-targeted AuNSs effectively attenuated arthritis progression without systemic side effects.

In Vitro and In Vivo Antitumor Activity of Indolo[2,3-b] Quinolines, Natural Product Analogs from Neocryptolepine Alkaloid.

Neocryptolepine (5-methyl-5H-indolo[2,3-b] quinoline) analogs were synthesized and evaluated in vitro and in vivo for their effect versus Ehrlich ascites carcinoma (EAC). The analogs showed stronger cytotoxic activity against EAC cells than the reference drug. The in vivo evaluation of the target compounds against EAC-induced solid tumor in the female albino Swiss mice revealed a remarkable decrease in the tumor volume (TV) and hepatic lipid peroxidation. A noticeable increase of both superoxide dismutase (SOD) and catalase (CAT) levels was reported (p < 0.001), which set-forth proof of their antioxidant effect. In addition, the in vitro antioxidant activity of the neocryptolepine analogs was screened out using the DPPH method and showed promising activities activity. The histopathological investigations affirmed that the tested analogs have a remarkable curative effect on solid tumors with minimal side-effect on the liver. The study also includes illustrated mechanism of the antitumor activity at the cell level by flow cytometry. The cell cycle analysis showed that the neocryptolepine analogs extensively increase the aggregation of tumor cells in three phases of the cell cycle (G0/G1, S and G2/M) with the emergence of a hypo-diploid DNA content peak (sub-G1) in the cell cycle experiments, which is a clear-cut for the apoptotic cell population. Furthermore, the immunological study manifested a significant elevation in splenic lymphocyte count (p < 0.001) with the elevation of the responsiveness of lymphocytes to phytohemagglutinin (PHA). These results indicate that these naturally-based neocryptolepine alkaloids exhibit marked antitumor activity in vivo and represent an important lead in the development of natural-based anticancer drugs.

Immunolocalization of MUC1 in chronic plaque psoriasis.

Psoriasis is a chronic skin inflammatory disease with immunological, hyperproliferative and angiogenic dysfunction. MUC1 is a molecular sensor and signal transductor that responds to external stimuli generating cellular responses, which include cell proliferation, growth, differentiation, migration, invasion, survival and secretion of growth factors, and cytokines. The current study aimed at evaluation of the possible role of MUC1 in the pathogenesis of psoriasis through its immunohistochemical localization in involved and uninvolved psoriatic skin compared to normal skin in addition of correlating MUC1 expression with the clinical and pathological parameters of psoriasis. The current study investigated 30 patients with psoriasis and 10 controls. MUC1 was expressed in epidermis in 30% of normal skin compared to 20% of uninvolved epidermis and 63.3% of involved epidermis of psoriatic skin. MUC1 was seen staining endothelial cells of capillaries and inflammatory cells in dermis in 10% of normal skin, 0% of uninvolved psoriasis, and 83.3% of involved psoriasis. Dermal expression of MUC1 in psoriasis was associated with mild to moderate degrees of epidermal acanthosis (p = .027). Intense MUC1 expression by psoriatic epidermis was associated with short disease duration (p = .044). The upregulation of MUC1 in involved psoriatic lesion compared to uninvolved and normal skin may suggest MUC1 role in pathogenesis of psoriasis especially early stages. MUC1 may be responsible for less severity of psoriasis in old aged patients.

Morphometric and ultrastructural analysis of tramadol effects on epididymis: an experimental study.

The effect of tramadol addiction on epididymal structure was not investigated before. Therefore, this experimental study was carried out to investigate the effect of chronic tramadol use on the epididymal structure using light and electron microscopies. Thirty adult Wister Albino male rats were divided into two groups: control group (five rats) and tramadol-treated group (25 rats), which was further subdivided into five subgroups that received tramadol orally at 4.5, 9, 45, 90, and 135 mg/kg/day, respectively, for 18 weeks. Epididymal tissues were dissected and processed for histopathological examination. Morphometric analysis showed significantly reduced mean values of epididymal ducts' diameters and epithelial height in the tramadol-treated group compared with the control group. Light microscopic examination revealed degeneration and necrosis of epididymal cells in the tramadol-treated group. Electron microscopic (EM) examination showed ultrastructure alterations in a dose-dependent manner. In conclusion, tramadol can adversely affect all epididymal cells, which subsequently deteriorate epididymal function and may affect sperm maturation, leading to subfertility.

Pleomorphic adenoma-like tumour of the breast.

AIMS: Pleomorphic adenoma (PA) of the breast is a rare tumour seen usually in postmenopausal women. Although PA of the salivary glands (SG) is recognized to be a benign tumour, the nature and biology of similar tumours seen in the breast remains to be defined. The aim of this study was to describe PA of the breast that was reported on core biopsy as an invasive matrix-producing metaplastic breast carcinoma (MBC). METHODS AND RESULTS: A core biopsy from a clinically malignant retroareolar mass showed mildly atypical polygonal cells with surrounding myxoid stroma. Immunohistochemistry showed expression of basal and luminal cytokeratins, but oestrogen receptor, human epidermal growth factor receptor 2 (HER2) and myoepithelial markers were negative. The excision specimen showed similar features, but in addition the stroma showed cartilage and bone. Also it was clear that the lesion was circumscribed and merged with a sclerosed papillary lesion consistent with what has been described as mammary PA. CONCLUSION: This lesion shows an overlap of morphology and immunophenotype with SG-PA and with MBC. The majority of mammary PAs have a benign behaviour, but local recurrence and development of carcinoma occur. We propose a new terminology of pleomorphic adenoma-like tumour of the breast to reflect the uncertain nature of these tumours and help guide management decisions.

Immunohistochemical expression of sperm-associated antigen 9 in nonmelanoma skin cancer.

Sperm-associated antigen 9 (SPAG9) is a scaffold protein for c-Jun-NH2-kinases, which play an important role in cell survival, proliferation, apoptosis, and tumor development. SPAG9 was claimed to be involved in the pathogenesis of carcinoma in different organs. The aim of this work was to investigate its role in the pathogenesis of nonmelanoma skin cancer (NMSC) through its immunohistochemical (IHC) localization in skin biopsies of these tumors. This retrospective and prospective study included 67 cutaneous specimens; 42 of NMSC [20 cases with basal cell carcinoma (BCC) and 22 cases with squamous cell carcinoma (SCC)] and 25 normal sun-exposed skin biopsies from age and gender-matched healthy subjects as a control group. SPAG9 expression was evaluated using standard IHC techniques. SPAG9 was expressed in 90% of BCC cases and in 81.8% of SCC cases. Positive expression in inflammatory cells was detected in 100% and 63.6% of BCC and SCC cases, respectively. Positive stromal expression was detected in 20% of BCC cases and was absent in all SCC cases. A significant negative correlation (r = -0.55, P = 0.008) was noted between SPAG9 H score and SCC histological grade and a significant association between SPAG9 H score and tumor grade was also detected where higher values were present in grade I tumors (P = 0.001). SPAG9 was upregulated in NMSC when compared with normal skin. In conclusion, SPAG9 is expressed in NMSC cases. It should be evaluated in large-scale studies to determine if it plays an active pathogenic role or its expression is an epiphenomenon not related to NMSC pathogenesis. Large-scale studies are warranted to determine its potential utility in guiding treatment decisions and following disease progression in theses cases. Its expression in normal skin needs further investigation.

Perforin expression in plaque psoriasis: an immunohistochemical study.

Psoriasis (PsO) is T-cell-mediated disease resulting from aberrant activation of both innate and adaptive immunity. Perforin is a multi-domain, pore-forming protein. It is located within the cytoplasm of CD 8 cytotoxic T cells (CTLs) and natural killer cells (NK). The aim of this study was to evaluate the immunohistochemical (IHC) expression of perforin in lesional and perilesional skin of chronic plaque psoriatic patient and correlate its expression with the standard clinico-pathological variables. This prospective case-control study was conducted on 50 PsO patients and 30 age- and gender-matched healthy subjects as a control group. There were high-significant differences between lesional and perilesional skin of plaque PsO patients as regards to IHC perforin status and localization (p < 0.001 for both). There was a high-significant difference between positive and negative perforin cases as regards to psoriasis area severity index (PASI) (p < 0.000). There were significant differences between mild and moderate-to-severe intensity of IHC perforin expression as regards to triggering factors and PASI (p = 0.02 and 0.03, respectively). Localization of IHC perforin positive lymphocytes in both epidermis and dermis was significantly associated with higher degree of acanthosis and higher degree of inflammatory infiltrates in comparison with positive cells located in dermis (p = 0.001 for both). Perforin might have a putative signaling in early and late plaque PsO. Plaque psoriatic patients with positive perforin expression could be a candidate for a future target therapy to stop the proposed scenario and achieve a therapeutic response.

Immunohistochemical Evaluation of Leptin Role in Skin Tags.

Skin tags (STs) are common benign dermal connective tissue neoplasms that are mainly composed of loose fibrous tissue. However, their exact etiology is not fully understood. Leptin is a major player in the biology and pathology of the skin and its appendages. It is linked to cell differentiation, proliferation, migration, and survival with pronounced effects on angiogenesis, blood flow, and tissue perfusion. This study aimed at investigating the possible role of leptin in STs pathogenesis and correlating its expression with different clinical and histopathological parameters. Using immunohistochemical techniques, we examined 90 subjects. These included 60 non-obese cases with STs and 30 age-, gender- and Body Mass Index-matched normal subjects as a control group. Leptin was overexpressed in STs compared with normal skin (p < .001). Nuclear and nucleocytoplasmic patterns were significantly associated with cases both in epidermis (p < .04) and dermis (p < .001). Higher epidermal leptin H score was significantly associated with female gender (p = .004) and haphazard collagen arrangement (p < .03). Higher dermal leptin H score was significantly associated with smooth skin tags (p = .01), dilated blood vessels (p = .04), presence of mast cells (MCs) (p = .002), presence of inflammatory cells (p = .004), and haphazard collagen arrangement (p < .001). In conclusion, leptin may play a role in STs pathogenesis through its effects on keratinocytes, fibroblasts and vascular endothelium. Further studies are recommended to clarify the molecular interplay between leptin and MCs in ST pathogenesis. Further studies are also needed to determine the significance of its nuclear expression.

Immunolocalization of glioma-associated oncogene homolog 1 in non melanoma skin cancer.

Glioma-associated oncogene homolog (GLI)1 is involved in controlling cell proliferation and angiogenesis. The aim of this work was to explore its possible role in non-melanoma skin cancer pathogenesis through its immunohistochemical (IHC) expression in skin biopsies of these diseases and correlating this expression with the clinico-pathological parameters of the studied cases. Seventy-six cutaneous specimens were studied; 30 cases with basal cell carcinoma (BCC), 30 cases with squamous cell carcinoma (SCC) and 16 normal skin samples, from age- and gender-matched subjects, as a control group. GLI1 was expressed in all BCC cases and in 60% of SCC cases. All SCC cases showed cytoplasmic, while 70% of BCC cases showed nucleocytoplasmic immunoreactivity. It was over expressed in BCC and SCC compared to normal skin (p = 0.01 and 0.0006, respectively). Higher Histo (H) score in BCC cases was significantly associated with female gender (p = 0.04), multiple lesions, desmoplastic stromal reaction and stromal angiogenesis (p < 0.001 for all). Higher H score in SCC cases was significantly associated with scalp location, nodular type, recurrent lesions, high tumor grade, lymphovascular invasion (p = 0.004 for all), inflammatory stromal reaction (p = 0.01), lymph node involvement and absence of calcification (p = 0.001 for both). In conclusion, GLI1 may play a role in BCC pathogenesis through its role in cell proliferation, migration, and angiogenesis. Its upregulation and cytoplasmic localization in SCC may suggest that its role in tumor pathogenesis is through mechanisms other than Hedgehog pathway activation. Further studies are needed to clarify the exact molecular basis of its oncogenic action.

Nuclear factor kappa B and cyclo-oxygenase-2: two concordant players in psoriasis pathogenesis.

Nuclear factor kappa B (NFκB) is a key regulatory element in a variety of immune and inflammatory pathways, cellular proliferation, differentiation and apoptosis. Cyclo-oxygenase 2 (COX2) is one of the downstream targets of NFκB. The current work aimed to explore the possible role of NFκB and COX2 in psoriasis pathogenesis through their immunohistochemical (IHC) expression in skin biopsies of this disease and correlating this expression with clinico-pathological parameters of studied cases. 103 subjects were studied; including 58 cases with psoriasis vulgaris (lesional and perilesional skin) and 45 normal, age- and gender-matched subjects, as a control group. NFκB and COX2 expressions were evaluated using standard IHC techniques. NFκB and COX2 were upregulated in psoriasis lesional skin compared to perilesional (p < 0.001 for both) and control skin (p < 0.001 for both). Higher NFκB and COX2 H scores were significantly associated with absent granular cell layer (p = 0.02 for both), severe degree of perivascular inflammatory infiltrate (p = 0.03 and 0.002, respectively) and thin suprapapillary epidermis (p = 0.003 and 0.006, respectively). Significant positive correlation was noted between NFκB and COX2 H scores in epidermis (r = 0.41, p = 0.02) and dermis (r = 0.6, p = 0.04) of lesional skin. Significant positive correlation between NFκB H score and PASI score (r = 0.38, p = 0.04) and between COX2 H score and PASI score (r = 0.52, p < 0.001) were detected in lesional epidermis. In conclusion, both NFκB and COX2 play a role in the pathogenesis of chronic plaque psoriasis. This may open an avenue for research for new therapeutic modalities based on their inhibition.

Neuro-folliculo-sebaceous cystic hamartoma is a unique entity.

Folliculosebaceous cystic hamartoma (FSCH) is a distinct type of cutaneous hamartoma of pilosebaceous origin that usually occurs on the face. For FSCH, other parts have been reported such as the genital area, and the trunk. A 50-year-old woman presented with an asymptomatic dome-shaped scalp nodule. The clinical diagnosis was pilar cyst or tumor. Histopathological assessment showed FSCH with absolute neural component as the only mesenchymal stroma, leading to the diagnosis of folliculosebaceous cystic neural hamartoma. To the best of our knowledge, absolute neural stroma in FSCH has not been reported previously in the literature.

Pleurotus ostreatus opposes mitochondrial dysfunction and oxidative stress in acetaminophen-induced hepato-renal injury.

BACKGROUND: Acetaminophen (APAP)-induced toxicity is a predominant cause of acute hepatic and renal failure. In both humans and rodents toxicity begins with a reactive metabolite that binds to proteins. This leads to mitochondrial dysfunction and nuclear DNA fragmentation resulting in necrotic cell death. Pleurotus ostreatus (an edible oyster mushroom) is well recognized as a flavourful food, as well as a medicinal supplement. In the present study, we evaluated the role of Pleurotus ostreatus in the protection against APAP-induced hepato-renal toxicity. We also explored the mechanism by which Pleurotus ostreatus exerts its effects. METHODS: Ninety adult male Swiss albino mice were divided into three groups (30 mice/group). Mice were offered normal diet (control and APAP groups), or diet supplemented with 10% Pleurotus ostreatus (APAP + Pleurotus ostreatus) for 10 days. Mice were either treated with vehicle (control group, single intra-peritoneal injection.), or APAP (APAP and APAP + Pleurotus ostreatus groups, single intra-peritoneal injection, 500 mg/kg), 24 hours after the last meal. RESULTS: APAP increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) glutamate dehydrogenase (GDH), creatinine, blood urea nitrogen (BUN), urinary kidney injury molecule-1 (KIM-1), and hepatic and renal malondialdehyde (MDA) content. APAP decreased hepatic and renal glutathione (GSH) content, as well as glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities. Supplementation with Pleurotus ostreatus significantly reduced APAP-induced elevated levels of ALT, AST, GDH, creatinine, BUN, KIM-1and MDA, while GSH level, and GSH-Px and SOD activities were significantly increased. Our findings were further validated by histopathology; treatment with Pleurotus ostreatus significantly decreased APAP-induced cell necrosis in liver and kidney tissues. CONCLUSIONS: We report here that the antioxidant effect of Pleurotus ostreatus opposes mitochondrial dysfunction and oxidative stress accompanying APAP over-dose, with subsequent clinically beneficial effects on liver and kidney tissues.

Immunolocalization of androgen receptor and estrogen receptors in skin tags.

Skin tags (STs) are benign connective tissue tumors of the dermis. Several clinical observations suggested the involvement of sex steroids in their development. This study aimed at investigating the possible role of androgen receptor (AR) and estrogen receptors (ERs) in STs pathogenesis through their immunohistochemical (IHC) localization in skin biopsies of this disease and to correlate their expression with different clinical and histopathological parameters. Using IHC techniques, we examined 62 cases with STs and 30 gender- and age-matched, healthy subjects, representing the control group. ERα, ERß, and AR were upregulated in STs compared to normal skin in epidermis and dermis (p < .001 for all). Higher AR H score was significantly associated with axillary STs (p = .02), skin colored tags (p = .03), acanthosis, and papillomatosis (p = .04 for both). Higher ERα H score was significantly associated with hyperpigmented tags (p < .001) and positive family history (p = .003). Higher ERß H score was significantly associated with female gender and obesity (p = .004 for both). Higher ERα and AR H scores were significantly associated with loose collagen arrangement (p = .02, p = .004, respectively). Higher AR, ERα, and ERß H scores were significantly associated with the presence of mast cells (p = .01, p = .04, p = .002, respectively) and dilated blood vessels (p = .006, p = .04, p = .04, respectively). In conclusion, AR and ERs may share in STs pathogenesis through their effect on keratinocytes, fibroblasts, and mast cells.

Hematopoietic stem cells: do they have a role in keloid pathogenesis?

Keloids are slow growing neoplasms characterized by benign proliferation of fibroblasts that is due, at least in part, to altered cytokine profiles. Stem cells were claimed to play a role in skin tumor development. However, their role in keloid formation is unclear. The current study investigated the immunoreactivity of CD34 and c-KIT antibodies in 30 cases with keloid lesions together with normal skin biopsies of 30, sex and age-matched subjects representing the control group. Examined keloid sections showed positive dermal stromal immunoreactivity for CD34 in 76.7% of cases. CD34 expression intensity and H score were upregulated in keloid tissue relative to normal skin (p < 0.0001, p = 0.0002, respectively) and in perilesional relative to lesional tissue (p = 0.03, p < 0.001, respectively). c-KIT showed positive dermal stromal expression in all cases. Dermal c-KIT expression intensity and H score were upregulated in keloid tissue relative to normal skin (p < 0.008, p < 0.001, respectively) and in perilesional relative to lesional tissue (p < 0.0001, p < 0.001, respectively). Lesional skin showed more staining of basal keratinocytes when compared to perilesional tissue (p < 0.0001). Hematopoietic stem cells may share in keloid pathogenesis. Further studies are warranted to gain firmer conclusion about the exact role played by these cells and the significance of their perilesional accumulation. The future therapy of keloid scars may have to target this stem cell population in order to deprive these tumors of their regenerative cell pools.

Impact of fungal load on diagnosis and outcome of allergic fungal rhinosinusitis.

Fungal load colonization may modify the classic eosinophilic inflammation in allergic fungal rhinosinusitis (AFRS). We aimed to evaluate the impact of fungal load on diagnosis and outcome of AFRS. In the present cohort study fungal load differences were determined prospectively according to Gomori methenamine silver (GMS) fungal stained (histopathological and cytological examination) with the tenacious mucus, cheesy clay-like materials and sinus mucosa/polyps in 12 AFRS patients. Two groups with different fungal loads, AFRS with (six patients) and without (six patients) high fungal loads (HFL) were evaluated for nasal endoscopic score, paranasal sinuses CT score, histopathological and immunohistochemical changes. Endoscopic outcome scoring differences were evaluated for 1 year after endoscopic sinus surgery and 1 month oral corticosteroids treatment. No differences were observed between both groups (AFRS with/without HFL) concerning the total CT score and opacification features (P > 0.05). Eosinophils and CD3 + CD8 + T cell were dominant in both groups. More edema and less fibrosis were observed in HFL group. Gliotoxin producers Aspergilli were present in all HFL in comparison to 5/6 (83.3%) in cases without HFL. Fewer patients 1/6 (16.6%) and less number of recurrences/year 0.1 ± 0.4 occurred in the AFRS with HFL compared to the AFRS without HFL [5/6 (83.3%) and 1.16 ± 0.7) (P = 0.021 and 0.023, respectively]. In addition to mucus and mucosal tissues, cheesy clay-like materials must be assessed in AFRS cases. Although patients of AFRS with HFL had negligible clinical differences from ordinary AFRS without HFL, they had better outcome after treatment.

Krox20 expression in abnormal scars: An immunohistochemical study.

BACKGROUND: Scars are the end outcome of healing. They are grouped into several types, the common of which are keloids, hypertrophic, and atrophic scars. The role of Krox20 in skin and hair physiology and pathology had emerged. Overexpression of Krox20 was sufficient to stimulate collagen gene expression and myofibroblast differentiation and is necessary for transforming growth factor-ß (TGF-ß) induced profibrotic responses. OBJECTIVE: To investigate the role of Krox20 in abnormal scar pathogenesis. Hopefully, this insight can set the route for newer therapeutic approaches. MATERIALS AND METHOD: This study was carried out on 30 cases (10 cases of keloids, 10 cases of atrophic scars, and 10 cases with hypertrophic scars [HTS]) and 10 age and gender-matched apparently healthy subjects as a control group. Thirty biopsies were taken from perilesional areas. Evaluation of Krox20 expression was done using standard immunohistochemical technique. RESULTS: Krox20 was downregulated in epidermis of scar biopsies compared with perilesional and normal skin (p = 0.02) while it was overexpressed in fibroblasts in lesional scar biopsies compared with perilesional and normal skin (p < 0.001). Keloid cases have significantly higher Krox20 expression in fibroblasts compared with HTS cases (p < 0.001). Krox20 had significantly nucleocytoplasmic pattern of staining in scar cases compared with normal skin (p < 0.001). CONCLUSION: Krox20 overexpression may have a role in scar pathogenesis through upregulation of multiple genes associated with tissue remodeling and wound healing. This may open an avenue for research for new therapies based on Krox20 inhibition.

Metformin alleviates neurocognitive impairment in aging via activation of AMPK/BDNF/PI3K pathway.

Slowing down age-related neurocognitive impairment has been a challenge. We evaluated the therapeutic effects of metformin in D-galactose-induced aging. Additionally, we studied the potential molecular mechanisms that could be responsible for metformin's anti-aging effects. Thirty male rats were equally divided into: 1-control group, which received saline solution, 2-D-galactose (D-gal) group, which received D-galactose (100 mg/kg/day) by gastric lavage for eight weeks, and 3-D-galactose + Metformin (D-gal + Met) treated group, which received D-galactose + metformin (200 mg/kg/day) by gastric lavage for eight weeks. Neurocognitive assessment was done. Measurement of inflammatory, oxidative stress, and BDNF biomarkers was performed. AMPK and PI3K genes expression were assessed. Hippocampal tissues were dissected for histopathological and immunohistochemical studies. D-gal resulted in neurocognitive impairments, elevation of inflammatory biomarkers, altered oxidative stress markers, decreased BDNF, decreased expression of synaptophysin and Bcl2 with increased expression of Caspase-3, and down-regulation of AMPK and PI3K genes. Neurodegenerative changes were present in the hippocampus. Metformin restored significantly D-gal induced neurodegenerative changes. We concluded that metformin could alleviate age-induced neurocognitive deficit via amelioration of neuroinflammation, attenuation of oxidative stress, reduction of apoptosis, as well as promotion of synaptic plasticity. These mechanisms could be mediated via the activation of the AMPK/BDNF/PI3K pathway.

Immunohistochemical expression of Axin-2, as an implication of the role of stem cell in scar pathogenesis and prognosis.

BACKGROUND: Wound healing is a multi-phased process. A disruption in these phases could result in a persistent wound or an atypical scar. Wounding activates wingless proteins (Wnt) signaling, which aids in the healing process. Axis inhibition protein-2 regulates a variety of cellular activities through the Wnt and other pathways. AIM: To assess the role of Axin-2 in patients with abnormal scars, using immunohistochemical study. METHODS: This case-control study enrolled a total of 60 participants: 30 patients with abnormal scars (12 hypertrophic scars, 13 atrophic scars, and 5 keloid scars) and 30 age, sex, and site matched, apparently healthy controls. For immunohistochemistry examination of Axin-2 expression, skin samples were obtained from (i) lesional and (ii) perilesional skin of patients with aberrant scars, as well as (iii) normal control's skin. RESULTS: Epidermal Axin-2 expression positivity, cellular topography, intensity, and H score showed significant differences between the groups (p < 0.05). In the dermis (fibroblast/myofibroblast), there were significant differences in Axin-2 expression positivity, location, intensity, and H score (p < 0.001 for all). The epidermal Axin-2 H score and the Manchester scale had a significant positive correlation (r = 0.832, p = 0.001). The epidermal Axin-2 H score and age (r = -0.576, p = 0.001), and the Stony Brook scale (r = -0.419, p = 0.021), had significant negative correlations. CONCLUSION: Axin-2 overexpression might be accused in pathogenesis of abnormal scar and clinical worse scar outcome. In order to deprive scars of their regenerative cell pools, future scar therapies may target Axin-2 as a stem cell marker.